Field of the Invention
The invention is directed to MtrE peptides, including chimeric peptides comprising the MtrE peptides, and their use in gonorrhea vaccines.
Background of the Invention
Gonorrhea is the second most frequently reported infection to the Center for Disease Control (CDC) and, as such, accrues significant public health costs. Similarly, gonorrhea is the second most commonly reported infection in the U.S. military. Gonorrhea, like all sexually transmitted infections (STIs), disproportionately occurs in adolescents and young adults; therefore diagnosis and treatment of gonorrhea significantly taxes the public health care system. Serious morbidity arises, primarily in women, due to ascension of gonococcal infection to the endometrium and fallopian tubes, which leads to pelvic inflammatory disease (PID). PID and the post-infection complications, chronic pelvic pain, infertility and ectopic pregnancy, also occur at high incidence in the U.S. and worldwide. Ectopic pregnancy is a life-threatening condition and the fourth leading cause of maternal death in the U.S. Another cause for concern is the demonstration that gonococcal infection is associated with a risk for increased transmission of the human immunodeficiency virus (HIV).
Current prevention strategies for gonorrhea are limited to safe-sex counseling and the identification and treatment of infected individuals. Alarmingly, antibiotic resistance emerges rapidly in Neisseria gonorrhoeae, which threatens the current control measures. Only one class of antibiotics, the extended spectrum cephalosporins (ESCs), is left to treat gonococcal infections and therefore, this pathogen recently reached “super bug” status in 2007 (CDC, 2007). Since then, decreased susceptibility to ESCs has been reported, and in 2009 an ESC-resistant N. gonorrhoeae strain was isolated in Japan (CDC, 2011; Unemo, et al, 2010). The inability to treat gonorrhea may soon become a reality. Therefore, there is an urgent need for a gonorrhea vaccine.
The gonococcal MtrC-MtrD-MtrE (MtrCDE) active efflux pump is critical for experimental genital tract infection of female mice. Mutants in this pump are the most attenuated of all the mutants we have tested in this model. MtrC and MtrD are periplasmic and inner membrane proteins, respectively. The MtrE subunit, in contrast, is located in the bacterial outer membrane. Based on homology to other RND pumps and in silico analysis of the predicted secondary structure of the MtrE protein, it is likely that MtrE has two surface-exposed loops that could possibly be targeted for a vaccine.